module 9 lipid management in hypertensive patients · module 9 lipid management in hypertensive...

Module 9 Lipid Management in Hypertensive Patients

Aims of this module

To provide recommendations on lipid management in adult hypertensive patients for primary prevention of cardiovascular disease (CVD) in primary care settingNote.

Screening

Screening of lipid profile should be performed for all newly diagnosed hypertensive patients, and as a part of the annual assessment1. This information, together with information on other risk factors, is useful in determining the individual’s cardiovascular risk and provides insight into the subsequent management.

Global risk assessment

In addition to hypertension and dyslipidaemia, there are other major cardiovascular risk factors, such as advancing age, male gender, cigarette smoking, obesity, physical inactivity, and family history of premature cardiovascular disease2. The total risk of developing CVD is determined by the combined effect of cardiovascular risk factors, which commonly coexist and act multiplicatively. An individual with several mildly raised risk factors may be at a higher total risk of CVD than someone with just one elevated risk factor3. Therefore, the global risk approach should be considered in every cardiovascular risk assessment including patients with hypertension. For all identified modifiable cardiovascular risk factors, they should be managed as possible. Periodic review of the cardiovascular risk is also necessary.

Note For lipid management in diabetic patients, please refer to Hong Kong Reference Framework for Diabetes

Care for Adults in Primary Care Settings.

1 HK Reference Framework for Hypertension Care for Adults in Primary Care Settings


Cardiovascular risk assessment Tools

Background Cardiovascular risk assessment tools aim at helping physicians to estimate the risk of cardiovascular events for individuals without known cardiovascular diseases, based on the presence of different risk factors. The predicted risk of an individual can be a useful guide for making clinical decisions on the intensity of interventions3, which should always be individualised. These multivariate cardiovascular risk assessment tools can usually be interpreted easily by referring simplified charts or tables, or by web-based calculators, and most of them can be accessed easily on the internet. There is currently no tool specifically designed for Chinese populations.

It has to emphasise that estimation of the cardiovascular risk is not necessary for individuals with known very high or high risk conditions (Table 1). Lipid lowering therapy should be considered for these individual unless contraindicated.

Table 1. Individuals at very high and high risk of developing future coronary events4

Risk level Clinical presentation of individuals Very high risk (1) Individuals with established coronary artery disease, atherosclerotic

cerebrovascular disease, aortic aneurysm or peripheral artery disease (2) Individuals with diabetes mellitus with chronic kidney disease (3) Individuals with familial hypercholesterolemia

High risk (1) Individuals with moderate to severe chronic kidney disease (estimated glomerular filtration rate [eGFR] <60ml/min/1.73 m2)

(2) Individuals with diabetes mellitus without established coronary artery disease, atherosclerotic cerebrovascular disease, aortic aneurysm, peripheral artery disease or chronic kidney disease

HK Reference Framework for Hypertension Care for Adults in Primary Care Settings 2


Examples of cardiovascular risk assessment tools (Table 2)

1. Framingham-based The original Framingham risk score (published in 1998) derived from Framingham

Heart Study5, a prospective cohort of largely Caucasian population, were widelyadapted worldwide, such as in National Cholesterol Education Program (NCEP)6,Joint British Societies 2 (JBS2)7 and the New Zealand Cardiovascular Risk Charts8;the former two guidelines had been widely used as reference in the public sectors inHong Kong (information as at Feb 2017)

The Framingham system had been recalibrated for Asian populations for differentcohorts, for example, Singapore-adapted Framingham Risk Score9: adjusted for Chinese, Malay and

Indian populations in Singapore Asia Pacific Cohort Studies Collaboration10: cohorts from Japan, Korea,

Singapore and China The Chinese Multi-Provincial Cohort Study11: Chinese cohorts from mainland

China It had been suggested that Framingham equation can be applied to the Hong Kong

Chinese population but requires recalibration in men due to overestimation of therisk12. There is currently no recalibrated tool available for local use

2. Systemic Coronary Risk Evaluation (SCORE)13

Based on European cohorts Recommended by European Society of Cardiology/ European Atherosclerosis

Society (ESC/EAS)14, 15

3. QRISK216

Based on patient data from England and Wales in the United Kingdom Included more medical variables such as type 2 diabetes, chronic renal disease, atrial

fibrillation, and rheumatoid arthritis Recommended by the National Institute of Clinical Excellence (NICE)17

4. Pooled Cohort Studies Equations18

Derived from Whites and African Americans cohorts Recommended by American College of Cardiology/ American Heart Association

(ACC/AHA)19

Study had questioned its validity in Hong Kong Chinese due to poor discriminationpower and calibration when applied to the Chinese population in Hong Kong12



Table 1. Examples of the cardiovascular risk assessment tools (information as at Feb 2017) Risk estimation system

Recommending guideline Variables Endpoint Remarks

Framingham- based

6 NCEP guidelines7 JBS2 guidelines

8 New Zealand guidelines Singapore guideline9

Sex, age, total cholesterol, HDL-C, SBP, smoking status, DM, HT treatment

10-year risk of CAD events (in original version)

NCEP and JBS2 guidelines are commonly used as reference in public sectors

SCORE13 ESC/EAS Guidelines for the management of

dyslipidaemias14

European Guidelines on cardiovascular disease

prevention in clinical practice15

Sex, age, total cholesterol or totalcholesterol/HDL-C ratio, SBP, smoking status

10-year risk of CVD mortality

QRISK216 NICE guidelines on lipid modification: cardiovascularrisk assessment and the modification of blood lipidsfor the primary and secondary prevention of

cardiovascular disease17

Sex, age, race, total cholesterol/HDL-C ratio, SBP, smoking status, DM, HT treatment, family history, BMI, chronic disease

10-year risk of CVD events

Pooled Cohort Studies Equations18

ACC/AHA guideline on the treatment of bloodcholesterol to reduce atherosclerotic cardiovascular

risk19

Sex, age, race (white or other/African American), total cholesterol, HDL-C, SBP, smoking status, DM, HT treatment

10-year risk for the first atherosclerotic CVD event

Poor Calibration for Hong Kong Chinese12

Abbreviations: BMI: Body mass index CAD: Coronary artery disease CVD: Cardiovascular disease DM: Diabetes mellitus HDL-C: High-density lipoprotein cholesterol HT: Hypertension LDL-C: Low-density lipoprotein cholesterol SBP: Systolic blood pressure



Treatment targets

The treatment target should be individualised for different patients. In general, the higher the cardiovascular risk, the more worthwhile to start lipid lowering therapy. For patients who have very high risk or high risk conditions (Table 1), lipid lowering therapy should be considered unless contraindicated. Many of the guidelines recommend different treatment goals for patients who have been stratified under different risk categories. There are also guidelines recommending the use of lipid lowering drugs for patients considered as high risk and do not recommend specific treatment targets. The treatment targets (if available) for primary prevention of some of the international guidelines are listed for reference in table 2.

For lipid management in diabetic patients, please refer to Hong Kong Reference Framework for Diabetes Care for Adults in Primary Care Settings.



Table 2. Treatment target levels of lipid (if available) for primary prevention in some of the international guidelines (information as at Feb 2017) Guideline Risk Category Lipid Target (if any)/ treatment strategies Remarks NCEP (2004)20

Low: 0-1 risk factor LDL-C < 4.1mmol/L Lipid targets are commonly used as reference in public sectors

Moderate: ≥ 2 risk factors and 10-year CHD risk < 10%

LDL-C < 3.4mmol/L

Moderately high: ≥ 2 risk factors and 10-year CHD risk 10 to < 20%

LDL-C < 3.4mmol/L (optional goal: < 2.6mmol/L)

High: CHD equivalent or 10-year CHD risk > 20%

LDL-C < 2.6mmol/L (optional goal: < 1.8mmol/L for very high risk)

JBS2 (2005)7

High: 10-year CVD risk ≥ 20% Optimal targets: LDL-C < 2.0mmol/L and TC < 4.0mmol/L, or 30% LDL-C reduction and 25% TCreduction Audit (minimum) standard: LDL-C < 3.0mmol/L and TC < 5.0mmol/L

Prediction charts are commonly used as reference in public sectors

New Zealand (2012 and 2013)21, 22

For original recommendation21, optimal targets were recommended. 5-year CVD risk > 15% LDL-C < 2.0mmol/L, TC < 4.0mmol/L, HDL-C ≥ 1.0mmol/L, TG <1.7mmol/L

Subsequent update22 does not recommended specific targets. TC ≥ 8mmol/L or TC:HDL-C ratio ≥ 8 Recommend drug treatment irrespective of CVD risk Combined CVD risk > 20% Recommend drug treatment Combined CVD risk 10-20% Shared decision-making approach on drug treatment

ACC/ AHA (2013)19

Recommends the use of high or moderate intensity statin in different risk. No recommendations on specific treatment targets. Primary LDL-C ≥ 4.9mmol/L High intensity statin Age 40-75 years without diabetes and 10-year ASCVD risk ≥ 7.5%

Moderate to high intensity statin

Remarks: Moderate-intensity statin: 30% to < 50% LDL-C reduction. High-intensity statin: ≥ 50% LDL-C reduction

(Table continued on next page)



Table 2. Treatment target levels of lipid (if available) for primary prevention in some of the international guidelines. (Continued) Guideline Risk Category Lipid Target (if any)/ treatment strategies Remarks NICE (2014)17

High: 10-year CVD risk ≥ 10% > 40% non-HDL-C reduction Fasting blood is not required for non-HDL-C

ESC/ EAS (2016)14

Moderate: • SCORE ≥ 1% to < 5%

LDL-C < 3.0mmol/L

High: • markedly elevated single risk

factors (e.g. familial dyslipidaemia, severe HT) or

• most other people with DM(some young people with type I diabetes may be at low or moderate risk) or

• moderate CKD or• SCORE ≥ 5% to < 10%

LDL-C < 2.6mmol/L. ≥ 50% reduction on LDL-C if baseline is between 2.6 and 5.1mmol/L

Very high: • documented CVD or• DM with target organ damage or• severe CKD or• SCORE ≥ 10%

LDL-C < 1.8mmol/L. ≥ 50% reduction on LDL-C if baseline is between 1.8 and 3.5 mmol/L

Abbreviations: ASCVD: Atherosclerotic cardiovascular disease CHD: Coronary heart disease CKD: Chronic kidney disease CVD: Cardiovascular disease DM: Diabetes mellitus HDL-C: High-density lipoprotein cholesterol HT: Hypertension LDL-C: Low-density lipoprotein cholesterol Non-HDL-C: Non high-density lipoprotein cholesterol TC: Total cholesterol TG: Triglycerides



Management

Dyslipidaemia can be modified by dietary change, increase in physical activity and lipid lowering drugs. In case of any secondary causes of dyslipidaemia such as hypothyroidism, diabetes, liver disease, nephrotic syndrome or steroid treatment, they should be identified and treated accordingly. Lifestyle modification is recommended in all hypertensive patients with dyslipidaemia. Use of lipid lower drugs should be commenced in patients who are considered having high cardiovascular risk or when lifestyle modification alone fails.

Lifestyle modification6, 14 Reduction of dietary fat intake Total fat <30% of total calorie/day Saturated fat <7%, cholesterol <200 mg, trans fat <1% of total calorie intake/day

Drug treatment (Figure 1) There are some patient groups who are more likely to discontinue their lipid-lowering medications after prescription. Recent studies performed in Hong Kong found that younger subjects (<50 years), patients who paid their first clinic visit and those without any comorbidities were more likely non-adherent or discontinuing their medications23,24. These subjects should receive more meticulous monitoring of their medication-taking behaviour.

(1) Statins (HMG - CoA reductase inhibitors) 25-27 ↓ LDL-C 25-55%, ↓TG 15-30%, ↑ HDL-C 5-10% 25-55% risk reduction in cardiovascular diseases (coronary heart disease, stroke) in

primary and secondary prevention studies Practical algorithm of statin usage is illustrated in Figure 1

(2) Fibrates 28 ↓ TG 25-50% + ↑ HDL-C 10-20% There is no strong evidence for using fibrate therapy in primary prevention of

cardiovascular disease. The use of fibrates in these patients should only be consideredwhen statins are contraindicated.

Gemfibrozil should not be initiated in patients on statin therapy because of an increasedrisk for muscle symptoms and rhabdomyolysis19. Fenofibrate is the preferred agent whenused in combination with statins but should be used with cautions and under closemonitoring

(3) Ezetimibe Can be used as an add-on drug in association with statins when the therapeutic target is

not achieved at the maximum tolerated statin dose, or as an alternative to statins inpatients who are intolerant of statins or with contraindications to statins4

No major adverse effects have been reported; the most frequent adverse effects aremoderate elevations of liver enzymes and muscle pain14



Figure 1. Practical algorithm of statin usage

Liver disease/ unexplained, persistent elevations of liver enzymes/ pregnant or lactating women

NO

Relat i ve c on traindications29 Conc om it a nt us e of cy c l os p or i ne , g e m f i br oz i l,

niacin, macrolide antibiotics, various antifungal agents, and cytochrome P-450 inhibitors

YES

Consider other treatment modalities

YES (Note: Combination of statin with drugs listed may carry an increase in risk o f myositis and liver derangement.) NO

Trade name of statins can be searched in https://www.drugoffice.gov.hk/eps/do/en/healthcare_providers/hom e.html Starting dose S imvastatin 10mg nocte / Pravastatin 10mg note / Atorvastatin 10mg daily / Rosuvastatin 5mg

O n titration of statins

f 0 Rule o Six3 : Doubling of dosage of statin will result in 6% LDL reduction but increasedrisk of transaminase elevation.

T he following demonstrates the doubling of dosage of statin:

S imvastatin31, 32 10mg 20mg 40mg Pravastatin33-36 10mg 20mg 40mg Atorvastatin37, 38 10mg 20mg 40mg 80mg Rosuvastatin39, 40 5mg 10mg 20mg L ovastatin41 10mg 20mg 40mg F luvastatin 20mg 40mg 80mg S ee Notes on hepatic side effects of statins

If LDL does not reach targets despite titration of statin or side effects develop on hi gher doses of statin, consider referral to specialist for combination lipid lowering th erapies with statin and other medications.

daily / Lovastatin 10mg daily / Fluvastatin 20mg daily

LDL not reaching targets

(Figure continued on next page)



Figure 1. Practical algorithm of statin usage (Continued)

Muscle Soreness/Tenderness/Pain29 Blood for CK only if muscle symptoms arise Increase in CK Rule out common causes like Exercise

/ Strenuous work Advise Moderation CK> 10x ULN STOP CK 3-10x ULN + symptoms STOP Progressive but asymptomatic CK elevation

Reduction in dose or temporary discontinuation29

AL T/AST29

Before start 12 weeks after start of

statin Thereafter repeat if

clinically indicated <3 x ULN careful

monitoring >/=3 x ULN STOP

Mon itoring-Laboratory Monitoring-Symptoms Headache and Dyspepsia29 Initial 6-8 weeks after therapy Each follow up

Abbreviations: ALT: Alanine transaminase AST: Aspartate aminotransferase

CK: Creatine kinase ULN: Upper limit of normal

Notes on hepatic side effects of statin: Elevated hepatic transaminase generally occurs in 0.5%-2% of cases and is dose

dependent42, 43, with relative risk 2 – 4 fold at higher doses of statin Progression to liver failure specifically due to statin is exceedingly rare if ever occurs44

Reversal of transaminase elevation is frequently noted with a reduction in dose, andelevations do not often recur with either re-challenge or selection of another statin45, 46



Simvastatin dose limitations When used with simvastatin, the following medications can raise the levels of simvastatin in the body and increase the risk of myopathy. Taking no more than the recommended dose of simvastatin with these medications will help keep simvastatin levels in the body at a safer level.

New simvastatin label

Contraindicated with simvastatin: • Itraconazole• Ketoconazole• Posaconazole (New)• Erythromycin• Clarithromycin• Telithromycin• HIV protease inhibitors• Nefazodone• Gemfibrozil• Cyclosporine• Danazol

Do not exceed 10 mg simvastatin daily with: • Verapamil• Diltiazem

Do not exceed 20 mg simvastatin daily with: • Amiodarone• Amlodipine (New)• Ranolazine (New)

Avoid large quantities of grapefruit juice (>1 quart daily)

FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. 15 Dec 2011.



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